# Cannabidiol sensitizes triple-negative breast cancer cells to NK cell-mediated killing via EGFR inhibition and FAS upregulation

## TL;DR

Cannabidiol (CBD) may help treat triple-negative breast cancer by making cancer cells more vulnerable to immune cells through specific molecular changes.

## Contribution

CBD is shown to sensitize TNBC cells to NK cell killing via EGFR inhibition and FAS upregulation, offering a novel therapeutic strategy.

## Key findings

- CBD significantly increased FAS protein expression in MDA-MB-468 cells compared to EGF treatment alone.
- CBD inhibited EGFR signaling by downregulating key oncogenic proteins such as KRAS, PI3K, and AKT.
- CBD enhanced NK cell-mediated cytotoxicity, reducing MDA-MB-468 cell viability more effectively than EGF alone.

## Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive subtype lacking targeted therapies, presenting a significant clinical challenge. The epidermal growth factor receptor (EGFR) plays a crucial role in TNBC progression, making it a promising target for therapeutic intervention. This study investigated the potential of cannabidiol (CBD) as a therapeutic agent that targets EGFR and associated signaling pathways in TNBC.

The TNBC cell lines MDA-MB-468 and MDA-MB-231 were treated with CBD in the presence or absence of epidermal growth factor (EGF). Cell proliferation, FAS protein expression, and activation of the EGFR signaling pathway were assessed. The cytotoxic effects of CBD on TNBC cells and natural killer (NK) cells were also evaluated.

CBD significantly elevated FAS protein expression in MDA-MB-468 cells compared to EGF treatment alone (125.29 ± 5.87% vs. 83.07 ± 1.30%, p < 0.0001). Further molecular analysis revealed that CBD inhibited EGFR signaling by downregulating key oncogenic proteins, including KRAS, PI3K, and AKT. Moreover, CBD enhanced the cytotoxic effects of NK-92 cells, reducing the viability of MDA-MB-468 cells more effectively than EGF alone did (52.12 ± 1.28% vs. 113.69 ± 1.68%, p < 0.0001).

These findings suggest that CBD holds promise as a potential anticancer agent in TNBC by disrupting EGFR signaling and promoting apoptosis. However, further studies are necessary to optimize its therapeutic window and minimize adverse effects, particularly regarding its potential cytotoxicity to immune cells.

The online version contains supplementary material available at 10.1186/s42238-025-00340-5.